The field of the invention is arsenical fluorescent agents and diagnostic assays.
Neglected Tropical Diseases (NTDs) are a group of infections that most commonly plague those who are extremely poor and live in remote rural areas, urban slums, and places of political conflict. Because they adversely affect child development, pregnancy, and worker productivity, NTDs are a major reason why many in developing nations cannot escape extreme poverty. Three such diseases are caused by trypanosomal parasites: Chagas' disease, African Trypanosomiasis or Sleeping Sickness, and Leishmaniasis.
While these diseases manifest in several clinical forms they are caused by a family of parasites with conserved biochemical machinery. We have exploited these similarities to develop a new diagnostic to be administered at the point of care (POC). In the case of these NTDs, the POC can be anywhere from a remote village along the Amazon to a forward operating base in Iraq. Thus, POC diagnostics must perform well in low technology settings with minimal requisite technical training. Since rapid and accurate diagnosis is critical for any disease control strategy, new diagnostics for these diseases are needed for better identification and monitoring of treatment populations.
There are two classes of diagnostics for these diseases: (1) parasitological methods that detect the parasite directly; these typically require observation of the parasite in blood samples under a microscope, and are labor intensive, time consuming, and are often inadequate for diagnosis in the chronic phase of infection when parasite levels in the blood are lower; and (2) immunological methods that rely on detection of markers from a patient's immune response; these methods are very sensitive but require highly trained technicians and expensive technology making them impractical for a field setting.
We have developed a new parasitological method that eliminates the need for trained personnel and expensive instrumentation, instead using a highly specific molecular sensor that can be detected with a handheld UV lamp or black light.
Immobilized monoarsenical [aminohexanoyl-4-aminophenylarsineoxide] supports have been described [Kalef et al., Anal Biochem. 1993 Aug. 1; 212(2):325-34; Kalef et al., Methods Enzymol. 1994, 233, 395-403] for the purification of proteins, and Adams et al., (J. Am. Chem. Soc., 2002, 124 (21), pp 6063-6076, 6068, col. 2, line 5) describes a a fluorescein with just one arsenic substituent, 4′-(1,3,2-dithiarsolan-2-yl)-5-carboxyfluorescein; see also, Hoffman et al., Nat. Protoc. 2010 September; 5(10):1666-77. Epub 2010 Sep. 23, “Fluorescent labeling of tetracysteine-tagged proteins in intact cells.”.